Stress also influences glutamate and dopamine(Drug information on dopamine), providing an environmental factor that appears to modulate neurotransmitter function (Palomo et al., 2004). Furthermore, dopamine dysregulation may also arise through a process of sensitization. Some individuals are particularly sensitive to the effects of certain drugs for either genetic reasons or as a result of early environmental damage. Thus, stresses such as drug use and social adversity in adolescence or early adult life may propel the neurodevelopmentally impaired individual over a threshold (Howes et al., 2004). These postnatal factors are notable for having an ongoing genetic component and demonstrating that early genetic and environmental factors do not appear to be sufficient by themselves to result in schizophrenia.
It is clear that many genes and environmental factors may not have direct neurological relationships, such as in the case of celiac disease. This multifactorial gastrointestinal disorder results in increased gut permeability and has been hypothesized to result in ingress of psychomimetic compounds increasing the risk for schizophrenia (Wei and Hemmings, 2005). Thus, external environmental effectors may require a specific genetic background in order to gain systemic access, allowing them to exert either direct or indirect regulatory effects on gene expression relevant to schizophrenia.
In summary, various genetic components of schizophrenia are beginning to be identified. This has important implications for designing drugs that can act as environmental modulators and/or for identifying potentially preventive measures that can be undertaken. Although we are receiving glimmers as to these underlying mechanisms, these first clues provide real hope for preventive, ameliorative and potentially direct treatment options for schizophrenia.
Dr. Picker directs the Metabolic Neurobehavioral Genetics Clinic at Children's Hospital Boston where he holds appointments in genetics and child psychiatry. He also has a research post at McLean Hospital.
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